Molecular characterization of piebaldism in a Tunisian family.

OBJECTIVE: The present study is aimed at performing the molecular characterization of a Tunisian family with piebaldism. METHODS: As the proband and her mother showed a severe phenotype, we first chose to screen exons 10, 11, 12, 13, 16, 17 and 18 of the KIT proto-oncogene by direct sequencing. RESULTS: Direct sequencing analysis showed a C to T substitution at 1939 in exon 13 (c.1939C>T) in heterozygous state in the patient and her mother. The mutation was not found in their unaffected family members or normal controls. CONCLUSION: Our results provide additional support that mutations in the tyrosine kinase domain of the KIT gene are responsible for the severe form of piebaldism.

[Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains]. / Recombinaison génétique chez le poliovirus vaccinal: étude comparative chez les souches excrétées en cours de vaccination par le vaccin poliomyélitique oral et les souches circulantes.

AIM OF STUDY: Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. MATERIAL AND METHODS: This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. RESULTS: Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. CONCLUSION: These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population.

High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis.

Xeroderma pigmentosum (XP, OMIM 278700-278780) is a group of autosomal recessive diseases characterized by hypersensitivity to UV rays. There are seven complementation groups of XP (XPA to XPG) and XPV. Among them, the XP group C (XP-C) is the most prevalent type in Western Europe and in the United States. We report here on the clinical and genetic investigation of XP-C patients in 14 Tunisian families. As the XPC V548A fs X572 mutation has been identified in Algerian and Moroccan populations, Tunisian patients were first screened for this mutation by a direct sequencing of exon 9 of the XPC gene. All patients with a severe clinical form had this mutation, thus showing the homogeneity of the mutational spectrum of XPC in Tunisia. A potential founder effect was searched and confirmed by haplotype analysis. Taking into account the similarity of the genetic background, we propose a direct screening of this mutation as a rapid and cost-effective tool for the diagnosis of XP-C in North Africa.

Histological characterization of Darier's disease in Tunisian families.

BACKGROUND: Darier's disease (OMIM 124200) is an autosomal-dominant skin disorder characterized by warty papules and plaques in seborreheic areas, palmo-plantar pits and distinctive nail abnormalities. The disease has complete penetrance in adults and variable expressivity. It is caused by mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase type 2 isoform (SERCA2). OBJECTIVE: We report histological investigations of six unrelated Tunisian families including 15 affected individuals with Darier's disease mutations. RESULTS: The typical histological features of Darier's disease have been observed in the 15 patients. Variable histological features have been observed among Tunisian patients ranging from mild to moderate lesions of Darier's disease. A significant correlation has been observed between the clinical presentation of the Darier's disease (mild or moderate) and the intensity of the histological features. Isolated acral form of Darier's disease was seen in one case. Two distinct original associations have been observed: Darier's disease/pemphigus vulgaris in one patient and Darier's disease/ichtyosis in the other patient. CONCLUSION: Our findings confirmed the clinical heterogeneity of Darier's disease on the basis of histological study. The intensity of the histological features could be closely correlated to the severity of Darier's disease clinical presentation.

Genetic features of polioviruses isolated in Tunisia, 1991-2006.

BACKGROUND: Genetic characterisation of polioviruses remains highly important even in countries where wild poliovirus circulation has been interrupted. Sequence data on representative wild strains from all geographical regions is required for surveillance purposes and surveillance for vaccine-related isolates with increased potential for transmissibility in humans should continue. OBJECTIVE: To report the genetic characteristics of wild and vaccine-related polioviruses isolated in Tunisia from 1991 to 2006. STUDY DESIGN: Wild isolates were sequenced in the VP1 genomic region and compared to each other. Vaccine-related isolates were assessed for genetic recombination by PCR/RFLP and sequence analysis of the 3D region. Recombinant viruses were assessed for genetic drift in the VP1 region. RESULTS: The VP1 sequences of the last wild isolates, all from serotype3, showed 97.7-98.7% nucleotide homology. Nineteen percent of vaccine-related isolates were vaccine/vaccine intertypic recombinants. No recombinant with non-poliovirus enteroviruses was identified. Mutational differences in the VP1 sequences of recombinant viruses ranged from 0.0% to 0.7% indicating a limited replication period. CONCLUSIONS: This study provides sequence data on wild polioviruses from Tunisia/North Africa and shows that in countries with continuous high vaccine coverage transmission of vaccine-related polioviruses is time-limited.

Involvement of granzyme B and granulysin in the cytotoxic response in lichen planus.

BACKGROUND: Lichen planus is an inflammatory dermatosis involving either skin and/or mucosal epithelial surfaces. A cell-mediated cytotoxicity response is the main suspected mechanism of this dermatosis. Granzyme B and granulysin are components of the cytoplasmic granules of cytotoxic T lymphocytes and natural killers. They are involved in cell-mediated apoptosis. This work studies the possible implication of granzyme B and granulysin in the cell-mediated cytotoxicity response in lichen planus. METHODS: In situ expression of granzyme B and granulysin was studied by real-time reverse transcriptase polymerase chain reaction in 15 biopsies of lichen planus. The distribution and the phenotype of the inflammatory infiltrate and the expression of granzyme B were studied by immunohistochemistry in seven other biopsies of lichen planus. RESULTS: Granzyme B and granulysin mRNA expression was one to two hundred times greater than in biopsies of normal skin. Immunohistochemical study revealed that the lymphohistiocytic infiltrate consisted mainly of CD4+ and CD8+ lymphocytes. Granzyme B+ cells were observed close to apoptotic keratinocytes. CONCLUSION: Our results suggest a central role for cell-mediated cytotoxicity by the granule exocytosis pathway probably because of auto-cytotoxic T-cell clones in the pathogenesis of lichen planus.

Supernumerary nipples in association with Hailey-Hailey disease in a Tunisian family.

Supernumerary nipples (SNs) or polythelia are developmental abnormalities of breast tissue. They are located along the embryonic mammary lines. Polythelia usually occurs as a sporadic abnormality, although familial aggregation has been occasionally reported. Hailey-Hailey disease is a rare autosomal genodermatosis characterized by disturbed keratinocyte adhesion. These cutaneous disorders have been described in correlation with many other abnormalities. We report here the association of Hailey-Hailey disease and supernumerary nipples in a Northern Tunisian family. To our knowledge, this is the first report of such a clinical association.

Enterovirus detection in stool specimen: relevance for poliovirus and enterovirus surveillance.

Detection of enterovirus genome by PCR in clinical samples is now extensively used for the diagnostic of enterovirus infections given its rapidity and high sensitivity. In contrast, its use in surveillance programs targeting specific enterovirus serotypes remains less frequent. The most sensitive protocols are those amplifying in the 5'untranslated region (5'UTR). However the possibility to use sequence analysis of the 5'UTR amplicons for serotype identification is not yet well established. In this report, stool samples from polio suspected cases and their healthy contacts were tested. The results of direct detection of enterovirus genome by PCR and serotype identification based on sequence analysis of the PCR products in the 5'UTR were compared to those of standard cell-culture-based protocols. Standard protocols detected enterovirus isolates in 7.4% of cases while 9.8% of samples were positive by PCR. Serotype identification based on sequence analysis of amplicons showed concordant results with serotypes determined on virus isolates by seroneutralisation or sequencing in the VP1 gene in 39% of cases only. These results confirm that the use of PCR amplification from stool samples improves the sensitivity of enterovirus detection but do not recommend the use of sequence analysis of the 5'UTR PCR product to determine enterovirus serotype.

[Seroprevalence of human parvovirus B19 in children with fever and rash in the North of Tunisia]. / Prévalence de l'infection par le parvovirus B19 humain au cours des éruptions fébriles de l'enfant dans le Nord tunisien.

The aim of the study is to evaluate the prevalence of specific antibodies anti-human parvovirus B19 (PVB19) immunoglobulin M (IgM) and IgG in children with fever and rash. This study involved 257 children aged from 7 months to 15 years with febrile rash unrelated to measles and rubella (seronegative for IgM). The sera were examined by immunoenzymatic assay. Detection of antibodies of PVB19 was done by enzyme-linked immunosorbent assay (Elisa). In our study, prevalence of immunoglobulin G (IgG) and IgM were 44 and 11.3%, respectively. Clinically, children with positive IgM serology had submitted an erythema infectiosum (13/29 cases), myocarditis (1 case), encephalitis (1 case), severe sickle cell anemia (7 cases), and immunocompromised (7 cases). The incidence rate of viral infection was 11.3%; most of the cases of PVB19 infection occurred between the months of May and August. Incidence was higher in the 10-15 years age group (21%). The prevalence of IgG antibody varied and increased with age, it rises from 38.2% in preschool children (19 months-4 years) to 53.5% in those aged between 4.5 and 15 years, reaching 58% in the 10-15 years age group. The four risk factors of PVB19 infection are: (1) those aged between 4.5 and 9 years, which is the most affected age group (P = 0.0018); (2) female gender in children aged between 19 months and 4 years (P = 0.037); (3) transfusion and (4) immune deficiency (P = 0.022 and P = 0.001, respectively). The study of the prevalence of PVB19 infection shows that viral infection is acquired early in childhood, increases with age; viral transmission is favored by the community life. Because of the widespread vaccination program against measles and rubella, the systematic search of PVB19 in front of eruptive fevers becomes important.

The role of Toll-like receptor 9 in gynecologic cancer.

Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis. TLR9 contributes to tumor regression by inducing cytotoxic T cell response (CTL), reducing the numbers of myeloid-derived suppressor cells (MDSCs), the tumor-associated macrophages (TAMs) and the regulatory T cells (T regs). It can however, also promote tumor progression and invasiveness of cervical tissue. Therefore, the dichotomous role of TLR9 needs to be carefully investigated in the setting of neoplastic disease.

[Colonic expression of gamma-interferon and interleukin-10 in Crohn's disease and ulcerative colitis]. / Expression colique de l'interféron-gamma et de l'interleukine-10 au cours de la maladie de Crohn et de la rectocolite ulcéro-hémorragique.

OBJECTIVE: The aim of this study was to investigate mucosal expression of INF-gamma and IL-10 in patients with Crohn's disease (CD) or ulcerative colitis (UC). METHODS: Fourteen patients with CD and 11 patients with ulcerative colitis participated and 7 healthy subjects were also included. Study of the mucosal expression of INF-gamma and IL-10 was conducted using biopsies from healthy and damaged colons, using the inverse transcription and genetic amplification (RT-PCR) technique in real time (Taqman). Our results were expressed as ratio between messenger cytokine (mRNA) levels and ribosomal RNA level of a reference molecule (rRNA 18S), then multiplied by 108. RESULTS: In the cases of Crohn's disease, the mucosa expressed increased INF-gamma and IL-10 compared with controls (respective medians: 23.03 vs. 1.87 p=0.04 and 20.61 vs. 2.13 p=0.08). A strong positive correlation was found in the mucosal expression of IL-10 and INF-gamma during CD (r=0.9 p<0.0001). In contrast, in patients with UC, the expression of INF-gamma and IL-10 were comparable to those observed in the controls (7.18 vs. 2.18 p=0.36 and 3.66 vs. 1.87 p=0.44). CONCLUSION: During Crohn's disease, the expression of both IL-10 and INF-gamma was increased and strongly correlated, compared with the controls.

Chronic iodine overload and apoptosis in cold nodules from endemic multinodular goiters.

As apoptosis and necrosis are known to exist during experimental goiter development and involution, we studied them in ten Tunisian multinodular endemic goiters, five of them having received a chronic excess of iodine during six months. Apoptotic thyrocyte nuclei have been counted on hematoxylin-eosin stained semi-thin sections. Using immunoperoxidase on paraffin sections, bcl-2 and bax immunoreactivities have been evidenced, and CD34 positive microvessels counted; ultra-thin sections have also been observed. After six months of iodine overload, apoptotic thyrocytes were ten times more numerous; CD34 positive endothelial cells were diminished by one half bcl-2 immunoreactivity disappeared in thyrocytes and a bax one appeared in thyroid follicular and endothelial cells. Presence of numerous apoptotic follicular and endothelial cells was confirmed using electron microscopy. Chronic iodine excess induces apoptosis and necrosis of thyroid follicular and endothelial cells, leading to thyroglobulin accumulation in connective tissue.

[Hereditary epidermolysis bullosa in Tunisia: an epidemio-clinical and ultrastructural study]. / Les epidermolyses bulleuses héréditaires en Tunisie: etude epidémio-clinique et ultra-structurale.

Hereditary epidermolysis bullosa (EB) are a group of genodermatoses whose common primary feature is formation of blisters following minor trauma. The aim of the present study was to assess epidemiological, clinical, genetical and histological particularities of patients with hereditary epidermolysis bullosa.

[Lanthanides and microanalysis. Effects of oral administration of two lanthanides: ultrastructural and microanalytical study]. / Lanthanides et microanalyse. Effets de l'administration orale de deux lanthanides :etude ultrastructurale et microanalytique.

The subcellular localization of cerium and lanthanum in the intestinal mucosa was studied after oral administration of cerium chloride or lanthanum chloride or lanthanum chloride followed 30 minutes after of cerium chloride to young adults Wistar rats. Two methods of observation and microanalysis were used. The transmission electron microscopy revealed the presence of dense electron granulations in the lysosmes of the duodenum enterocyte, when these elements were administrated simultaneously. The ion mass microanalysis permits to detect the presence of La and Ce as bright points outlining the intestinal villi. These points correspond to the lysosomes containing the granulations previously described. These granulations are formed by the cerium and the lanthanum associated to the phosphor and forming probably insoluble salts of Ce/La phosphate.

[A case of subcutaneous dirofilariasis in Tunisia]. / Un cas de dirofilariose sous-cutanée en Tunisie.

The authors report a case of Scrotal subcutaneous dirofilariasis in man for the first time in Tunisia. The diagnosis was established by pathological examination of a biopsy but the identification of the species was not possible. Surgical exeresis of the node was followed by a complete recovery.

[Tracheopathia osteochondroplastica associated with a liver hydatic cyst broken in bronchi]. / Trachéopathie ostéochondroplastique associée à un kyste hydatique du foie fistulisé dans les bronches.

Tracheobronchopathia osteochondroplastica (TBOC) is an unusual respiratory disorder characterized by cartilaginous or bony mucosal nodules in the tracheobronchial tree. It mainly affects men over 50 years old and clinical manifestations are observed when obstructive or infectious complications occur. We report a case of tracheopathia osteoplastica of the upper third of the trachea in a young 35-year-old mal, fortuitously discovered while exploring a biliptysis caused by a broken hydatic cyst of the liver. TBOC can be associated with various metabolic, inflammatory and neoplastic disorders, but its pathogenesis remains unknown. A metaplastic origin is actually the main hypothesis proposed.

[Minimal deviation adenocarcinoma of the uterine cervix in a woman with Peutz-Jeghers syndrome. Report of a case]. / Adénocarcinome à déviation minime du col utérin chez une femme porteuse d'un syndrome de Peutz-Jeghers. A propos d'une observation.

We report a case of minimal deviation adenocarcinoma of the uterine cervix in a 32 year old women who present a Peutz Jeghers syndrome. This patient also had fibroadenoma of the breast and dystrophic mastopathy. This case represent an example of predisposition to developing tumors of the Peutz Jeghers syndrome.

[Aggressive angiomyxoma of the perineum and pelvis. A report of two cases with pelvic and para-testicular localization]. / Angiomyxome agressif périnéo-pelvien. A propos de deux observations de localisation pelvienne et paratesticulaire.

Two cases of aggressive angiomyxoma of the pelvis and perineum are described; the first occurred in 32 year old woman who had a vulvar mass, the second in a 78 year old man who presented inguinal hernia. This recently described entity is characterized by its microscopic appearance (low cellularity, loose myxoid stroma and prominent vascular component), and propensity to local aggressivity, and common recurrence after surgery.

[Small intestine occlusion caused by the silent opening of liver hydatid cysts into the peritoneum. Apropos of an uncommon case]. / Occlusion du grêle par ouverture de Kystes hydatiques du foie dans le péritoine à bas bruit. A propos d'un cas exceptionnel.

The authors report one exceptional case of organic small bowel occlusion. The etiological diagnosis was performed by ultrasonographic examination and showed two hydatid cysts of the liver opened into the peritoneum and a peritoneal fluid collection corresponding to the hydatid fluid. The authors emphasize the absence of clinical symptoms during the opening of the hydatid cysts of the liver into the peritoneum and the usefulness of emergency ultrasonographic examination of the entire abdomen in cases of small bowel obstruction without any evident etiology.